Vacuum drying of active pharmaceutical ingredients (API) is an energy‐intensive process that is often a manufacturing bottleneck. A multiphase transport model to predict drying performance under the assumption that boiling is the dominant mechanism is developed. Laboratory scale drying experiments were performed over a range of temperatures and pressures using acetone as the solvent and glass beads of three different particle sizes to mimic APIs. A two‐phase transport model with the vapor and solid considered as one phase and the liquid treated as the second phase was capable of qualitatively reproducing the drying dynamics is found. Adjustable model parameters estimated from experimental data collected over a range of operating conditions exhibited trends that provided further insight into drying behavior. Boiling is the dominant mechanism in vacuum drying and our transport model captured the key physics of the process. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3639–3655, 2015